WO2016073476A1

WO2016073476A1 - Systems and methods for lesion assessment

Info

Publication number: WO2016073476A1
Application number: PCT/US2015/058824
Authority: WO
Inventors: Omar Amirana; Kenneth C. Armstrong; James H. Bowen; Cinnamon Larson; Marco A. MERCADER; Terrance J. RANSBURY; Narine SARVAZYAN
Original assignee: The George Washington University; LuxCath, LLC
Priority date: 2014-11-03
Filing date: 2015-11-03
Publication date: 2016-05-12
Also published as: KR20170116005A; CN113143440A; US10722301B2; EP3215002A1; EP3215002B1; CN113143440B; JP2017537681A; US20200352645A1; KR102499045B1; EP3215002A4; AU2015343258B2; AU2015343258A1; US11559352B2; CN107613849A; JP2021104333A; JP7178053B2; US20160120599A1; CN107613849B

Abstract

Ablation visualization and monitoring systems and methods are provided. In some embodiments, such methods comprise applying ablation energy to a tissue to form a lesion in the tissue, illuminating the tissue with a light to excite NADH in the tissue, wherein the tissue is illuminated in a radial direction, an axial direction, or both, monitoring a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level, and stopping ablation of the tissue when the level of NADH fluorescence reaches the predetermined lower level.

Description

SYSTEMS AND METHODS FOR LESION ASSESSMENT

RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application Serial No. 62/074,619, filed on November 3, 2014, which is incorporated herein by reference in its entirety.

FIELD

[0002] The present disclosure generally relates to ablation visualization and monitoring systems and methods.

BACKGROUND

[0003] Atrial fibrillation (AF) is the most common sustained arrhythmia in the world, which currently affects millions of people. In the United States, AF is projected to affect 10 million people by the year 20S0. AF is associated with increased mortality, morbidity, and an impaired quality of life, and is an independent risk factor for stroke. The substantial lifetime risk of developing AF underscores the public heath burden of the disease, which in the U.S. alone amounts to an annual treatment cost exceeding $7 billion.

[0004] Most episodes in patients with AF are known to be triggered by focal electrical activity originating from within muscle sleeves that extend into the Pulmonary Veins (P V). Atrial fibrillation may also be triggered by focal activity within the superior vena cava or other atrial structures, i.e. other cardiac tissue within the heart's conduction system. These focal triggers can also cause atrial tachycardia that is driven by reentrant electrical activity (or rotors), which may then fragment into a multitude of electrical wavelets that are characteristic of atrial fibrillation. Furthermore, prolonged AF can cause functional alterations in cardiac cell membranes and these changes further perpetuate atrial fibrillation.

[0005] Radiofrequency ablation (RFA), laser ablation and cryo ablation are the most common technologies of catheter-based mapping and ablation systems used by physicians to treat atrial fibrillation. Physicians use a catheter to direct energy to either destroy focal triggers or to form electrical isolation lines isolating the triggers from the heart's remaining conduction system. The latter technique is commonly used in what is called pulmonary vein isolation (PYI). However, the success rate of the AF ablation procedure has remained relatively stagnant with estimates of recurrence to be as high as 30% to 50% one-year post procedure. The most common reason for recurrence after catheter ablation is one or more gaps in the PVI lines. The gaps are usually the result of ineffective or incomplete lesions that may temporarily block electrical signals during the procedure but heal over time and facilitate the recurrence of atrial fibrillation.

[0006] PV isolation (PVI) can be accomplished in most patients using irrigated ablation catheters, however recurrence of AF may occur over time. Recurrences are thought to be due to PV reconnections from sites that either recovered, gaps in the ablation lines, or ablated sites that did not achieve transmurality during the initial procedure. Therefore, lesion assessment is very important in catheter ablation procedures so that the operator can deliver the best possible lesions during pulmonary vein isolation procedures. The improved quality of the lesions can reduce atrial fibrillation recurrences.

[0007] Real-time optical tissue characterization can provide excellent and previously impossible assessment of electrode-tissue contact and lesion progression during ablation. It can also provide highly valuable information regarding the myocardium, collagen, elastin tissue composition at the site of catheter tip and represents a new frontier in the understanding of the complex nature of the biophysics of cardiac ablation. Lesion depth directly correlates to a decrease in fNADH signal intensity. This information should be used to optimize the selection of ablation power and ablation energy application time to maximize lesion formation and improve the success of ablation procedures. Therefore, there is a need for systems and methods for real-time optical tissue characterization.

SUMMARY

[0008] Ablation visualization and monitoring systems and methods are provided.

[0009] According to some aspects of the present disclosure, there is provided a method that includes applying ablation energy to a tissue to form a lesion in the tissue, iUuminating the tissue with light energy (such as, for example, UV light) to excite NADH in the tissue, wherein the tissue is illuminated in a radial direction, an axial direction, or both, monitoring a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level, and stopping ablation of the tissue when the level of NADH fluorescence reaches the predetermined lower level.

[0010] According to some aspects of the present disclosure, there is provided a system for monitoring tissue ablation that includes a catheter comprising a catheter body and a distal tip positioned at a distal end of the catheter body, the distal tip defining an illumination cavity having one or more openings for exchange of light energy between the illumination cavity and tissue, an ablation system in communication with the distal tip to deliver ablation energy to distal tip, a visualization system comprising a light source, a light measuring instrument, and one or more optical fibers in communication with the light source and the light measuring instrument and extending through the catheter body into the illumination cavity of the distal tip, wherein the one or more optical fibers are configured to pass light energy in and out of the illumination chamber, and a processor in communication with the ablation energy source, light source and the light measuring instrument, the processor being programmed to collect light reflected from a tissue illuminated with light energy (such as, for example, UV light) to excite NADH in the tissue, while ablation energy is being applied to the tissue to form a lesion in the tissue; monitor a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level; and cause ablation of the tissue to stop when the level of NADH fluorescence reaches the predetermined lower level.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The presently disclosed embodiments will be further explained with reference to the attached drawings, wherein like structures are referred to by like numerals throughout the several views. The drawings shown are not necessarily to scale, with emphasis instead generally being placed upon illustrating the principles of the presently disclosed embodiments.

[0012] FIG. 1 A illustrates an embodiment of an ablation visualization and monitoring system of the present disclosure.

[0013] FIG. IB is a diagram of an embodiment of a visualization system for use in connection with an ablation visualization and monitoring system of the present disclosure.

[0014] FIG. 1C illustrates an exemplary computer system suitable for use in connection with the systems and methods of the present disclosure.

[0015] FIGS. 2A-2E illustrate various embodiments of catheters of the present disclosure.

[0016] FIG. 3 illustrates exemplary fluorescence spectral plots for monitoring contact between a catheter and tissue according to the present disclosure.

[0017] FIG. 4 illustrates exemplary spectral plots of various tissue compositions. [0018] FIG. 5 and FIG. 6 illustrate plots of fNADH over time during formation of endocardial lesions and epicardial lesions, respectively.

[0019] FIG. 7A, FIG. 7B and FIG. 7C illustrate exemplary fluorescence spectral plots for monitoring stability of a catheter according to the present disclosure.

[0020] FIG. 8A and FIG. 8B illustrate exemplary fNADH signal as the catheter traverses from healthy tissue to the margin of a lesion and then to the center of a lesion.

[0021] FIG. 9 is a graph comparing fNADH and Impedance over time during an application of ablation energy.

[0022] While the above-identified drawings set forth presently disclosed embodiments, other embodiments are also contemplated, as noted in the discussion. This disclosure presents illustrative embodiments by way of representation and not limitation. Numerous other modifications and embodiments can be devised by those skilled in the art which fall within the scope and spirit of the principles of the presently disclosed embodiments.

DETAILED DESCRIPTION

[0023] The present disclosure provides methods and systems for lesion assessment. In some embodiments, the system of the present disclosure includes a catheter configured to serve two functions: a therapeutic function of delivering ablation therapy to a target tissue and a diagnostic function of gathering a signature spectrum from a point of contact of the catheter and tissue to access lesions. In some embodiments, the systems and methods of the present disclosure may be employed for imaging tissue using nicotinamide adenine dinucleotide hydrogen (NADH) fluorescence (fNADH). In general, the system may include a catheter with an optical system for exchanging light between tissue and the catheter. In some embodiments, the instant systems allow for direct visualization of the tissue's NADH fluorescence, or lack thereof, induced by ultraviolet (UV) excitation. The NADH fluorescence signature returned from the tissue can be used to determine the quality of contact between the tissue and a catheter system.

[0024] In some embodiments, the catheter includes an ablation therapy system at its distal end and is coupled to a diagnostic unit comprising a light source, such as a laser, and a spectrometer. The catheter may include one or more fibers extending from the light source and the spectrometer to a distal tip of the catheter to provide illuminating light to the point of contact between the catheter and tissue and to receive and deliver a signature NADH spectrum from the point of contact to the spectrometer. The signature NADH spectrum may be used to assess a lesion in the target tissue. In some embodiments, the methods of the present disclosure include illuminating a tissue having a lesion, receiving a signature spectrum of the tissue, and performing a qualitative assessment of the lesion based on the signature spectrum from the tissue. The analysis can occur in real-time before, during and after ablation lesion formation. It should be noted that while the systems and methods of the present disclosure are described in connection with cardiac tissue and NADH spectrum, the systems and methods of the present disclosure may be used in connection with other types of tissue and other types of fluorescence.

[002S] System: Diagnostic imit

[0026] In reference to FIG. 1 A, the system for providing ablation therapy 100 may include an ablation therapy system 110, a visualization system 120, and a catheter 140. In some embodiments, the system 100 may also include one or more of an irrigation system 170, ultrasound system 190 and a navigation system 200. The system may also include a display 180, which can be a separate display or a part of the visualization system 120, as described below. In some embodiments, the system includes an RF generator, an irrigation pump 170, an irrigated-tip ablation catheter 140, and the visualization system 120.

[0027] In some embodiments, the ablation therapy system 110 is designed to supply ablation energy to the catheter 140. The ablation therapy system 110 may include one or more energy sources that can generate radiofrequency (RF) energy, microwave energy, electrical energy, electromagnetic energy, cryoenergy, laser energy, ultrasound energy, acoustic energy, chemical energy, thermal energy or any other type of energy that can be used to ablate tissue. In some embodiments, the catheter 140 is adapted for an ablation energy, the ablation energy being one or more of RF energy, cryo energy, laser, chemical, electroporation, high intensity focused ultrasound or ultrasound, and microwave.

[0028] In reference to FIG. IB, the visualization system 120 may include a light source 122, a light measuring instrument 124, and a computer system 126.

[0029] In some embodiments, the light source 122 may have an output wavelength within the target fluorophore (NADH, in some embodiments) absorption range in order to induce fluorescence in healthy myocardial cells. In some embodiments, the light source 122 is a solid-state laser that can generate UV light to excite NADH fluorescence. In some embodiments, the wavelength may be about 355nm or 355 nm +/- 30 ran. In some embodiments, the light source 122 can be a UV laser. Laser-generated UV light may provide much more power for illumination and may be more efficiently coupled into a fiber-based Ulumination system, as is used in some embodiments of the catheter 140. In some embodiments, the instant system can use a laser with adjustable power up to ISO mW.

[0030] The wavelength range on the light source 122 may be bounded by the anatomy of interest, or a user specifically choosing a wavelength that causes maximum NADH fluorescence without exciting excessive fluorescence of collagen, which exhibits an absorption peak at only slightly shorter wavelengths. In some embodiments, the light source 122 has a wavelength from 300nm to 400nm. In some embodiments, the light source 122 has a wavelength from 330nm to 370nm. In some embodiments, the light source 122 has a wavelength from 330nm to 355nm. In some embodiments, a narrow-band 355 nm source may be used. The output power of the light source 122 may be high enough to produce a recoverable tissue fluorescence signature, yet not so high as to induce cellular damage. The light source 122 may be coupled to an optical fiber to deliver light to the catheter 140, as will be described below.

[0031] In some embodiments, the systems of the present disclosure may utilize a spectrometer as the light measuring instrument 124. In some embodiments, the light measuring instrument 124 may comprise a camera connected to the computer system 126 for analysis and viewing of tissue fluorescence. In some embodiments, the camera may have high quantum efficiency for wavelengths corresponding to NADH fluorescence. One such camera is an Andor iXon DV860. The spectrometer 124 may be coupled to an imaging bundle that can be extended into the catheter 140 for visualization of tissue. In some embodiments, the imaging bundle for spectroscopy and the optical fiber for illumination may be combined. An optical bandpass filter of between 435nm and 485nm, in some embodiments, of 460nm, may be inserted between the imaging bundle and the camera to block light outside of the NADH fluorescence emission band. In other words, a Miter having a center wavelength of 460 nm with a 50 nm bandwith may be utilized. In some embodiments, other optical bandpass filters may be inserted between the imaging bundle and the camera to block light outside of the NADH fluorescence emission band selected according to the peak fluorescence of the tissue being imaged. [0032] In some embodiments, the light measuring instrument 124 may be a CCD (charge- coupled device) camera. In some embodiments, the spectrometer 124 may be selected so it is capable of collecting as many photons as possible and that contributes minimal noise to the image. Usually for fluorescence imaging of live cells, CCD cameras should have a quantum efficiency at about 460 urn of at least between 50-70%, indicating that 30-50% of photons will be disregarded. In some embodiments, the camera has quantum efficiency at 460 nm of about 90%. The camera may have a sample rate of 80 KHz. In some embodiments, the spectrometer 124 may have a readout noise of 8 e- (electrons) or less. In some embodiments, the spectrometer 124 has a minimum readout noise of 3e-. Other light measuring instruments may be used in the systems and methods of the present disclosure.

[0033] The optical fiber can deliver the gathered light to a long pass filter that blocks the reflected excitation wavelength of 355nm, but passes the fluoresced light that is emitted from the tissue at wavelengths above the cutoff of the filter. The filtered light from the tissue can then be captured and analyzed by the light measuring instrument 124. The computer system 126 acquires the information from the light measuring instrument 124 and displays it to the physician.

[0034] In some embodiments, the digital image that is produced by analyzing the light data may be used to do the 2D and 3D reconstruction of the lesion, showing size, shape and any other characteristics necessary for analysis. In some embodiments, the image bundle may be connected to the light measuring instrument 124, which may generate a digital image of the lesion being examined from NADH fluorescence (fNADH), which can be displayed on the display 180. In some embodiment, these images can be displayed to the user in real time. The images can be analyzed by using software to obtain real-time details (e.g. intensity or radiated energy in a specific site of the image) to help the user to determine whether further intervention is necessary or desirable. In some embodiments, the NADH fluorescence may be conveyed directly to the computer system 126.

[0035] In some embodiments, the optical data acquired by the light measuring instrument 124 can be analyzed to provide information about lesions during and after ablation including, but not limited to lesion depth and lesion size. In some embodiments, data from the light measuring instrument can be analyzed to determine if the catheter 140 is in contact with the myocardial surface and how much pressure is applied to the myocardial surface by the tip of the catheter. In some embodiments, data from the light measuring instrument 124 is analyzed to determine the presence of collagen or elastin in the tissue. In some embodiments, data from the light measuring instrument is analyzed and presented visually to the user via a graphical user interface in a way that provides the user with real-time feedback regarding lesion progression, lesion quality, myocardial contact, tissue collagen content, and tissue elastin content.

[0036] Referring back to FIG. 1A, in some embodiments, the system 100 of the present disclosure may further include an ultrasound system 190. The catheter 140 may be equipped with ultrasound transducers in communication with the ultrasound system 190. In some embodiments, the ultrasound may show tissue depths, which in combination with the metabolic activity or the depth of lesion may be used to determine if a lesion is transmural or not. In some embodiments, the ultrasound transducers may be located in the distal section of the catheter 140, and optionally in the tip of the distal electrode. The ultrasonic transducers may be configured to assess a tissue thickness either below or adjacent to the catheter tip. In some embodiments, the catheter 140 may comprise multiple transducers adapted to provide depth information covering a situation where the catheter tip is relatively perpendicular to a myocardium or relatively parallel to a myocardium.

[0037] Referring to FIG. 1A, as noted above, the system 100 may also include an irrigation system 170. In some embodiments, the irrigation system 170 pumps saline into the catheter 140 to cool the tip electrode during ablation therapy. This may help to prevent steam pops and char (i.e. clot that adheres to the tip that may eventually dislodge and cause a thrombolytic event) formation. In some embodiments, the irrigation fluid is maintained at a positive pressure relative to pressure outside of the catheter 140 for continuous flushing of the one or more openings 154.

[0038] Referring to FIG. 1A, the system 100 may also include a navigation system 200 for locating and navigating the catheter 140. In some embodiments, the catheter 140 may include one or more electromagnetic location sensors in communication with the navigation system 200. In some embodiments, the electromagnetic location sensors may be used to locate the tip of the catheter in the navigation system 200. The sensor picks up electromagnetic energy from a source location and computes location through triangulation or other means. In some embodiments the catheter 140 comprises more than one transducer adapted to render a position of the catheter body 142 and a curvature of the catheter body on a navigation system display. In some embodiments, the navigation system 200 may include one or more magnets and alterations in the magnetic field produced by the magnets on the electromagnetic sensors can deflect the tip of catheters to the desired direction. Other navigation systems may also be employed, including manual navigation.

[0039] The computer system 126 can be programed to control various modules of the system 100, including, for example, control over the light source 122, control over the light measuring instrument 124, execution of application specific software, control over ultrasound, navigation and irrigation systems and similar operations.

[0040] FIG. 1C shows, by way of example, a diagram of a typical processing architecture 308, which may be used in connection with the methods and systems of the present disclosure. A computer processing device 340 can be coupled to display 340AA for graphical output. Processor 342 can be a computer processor 342 capable of executing software. Typical examples can be computer processors (such as Intel® or AMD® processors), ASICs, microprocessors, and the like. Processor 342 can be coupled to memory 346, which can be typically a volatile RAM memory for storing instructions and data while processor 342 executes. Processor 342 may also be coupled to storage device 348, which can be a non-volatile storage medium, such as a hard drive, FLASH drive, tape drive, DVDROM, or similar device. Although not shown, computer processing device 340 typically includes various forms of input and output The I/O may include network adapters, USB adapters, Bluetooth radios, mice, keyboards, touchpads, displays, touch screens, LEDs, vibration devices, speakers, microphones, sensors, or any other input or output device for use with computer processing device 340. Processor 342 may also be coupled to other type of computer-readable media, including, but are not limited to, an electronic, optical, magnetic, or other storage or transmission device capable of providing a processor, such as the processor 342, with computer-readable instructions. Various other forms of computer- readable media can transmit or carry instructions to a computer, including a router, private or public network, or other transmission device or channel, both wired and wireless. The instructions may comprise code from any computer-programming language, including, for example, C, C++, C#, Visual Basic, Java, Python, Perl, and JavaScript

[0041] Program 349 can be a computer program or computer readable code containing instructions and/or data, and can be stored on storage device 348. The instructions may comprise code from any computer-programming language, including, for example, C, C++, C#, Visual Basic, Java, Python, Perl, and JavaScript. In a typical scenario, processor 204 may load some or all of the instructions and/or data of program 349 into memory 346 for execution. Program 349 can be any computer program or process including, but not limited to web browser, browser application, address registration process, application, or any other computer application or process. Program 349 may include various instructions and subroutines, which, when loaded into memory 346 and executed by processor 342 cause processor 342 to perform various operations, some or all of which may effectuate the methods for managing medical care disclosed herein. Program 349 may be stored on any type of non-transitory computer readable medium, such as, without limitation, hard drive, removable drive, CD, DVD or any other type of computer-readable media.

[0042] In some embodiments, the computer system may be programmed to perform the steps of the methods of the present disclosure and control various parts of the instant systems to perform necessary operation to achieve the methods of the present disclosure. In some embodiments, the processor may be programmed to collect light reflected from a tissue illuminated with a UV light to excite NADH in the tissue, while ablation energy is being applied to the tissue to form a lesion in the tissue; monitor a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level; and cause (either automatically or by prompting the user) ablation of the tissue to stop when the level of NADH fluorescence reaches the predetermined lower level. In some embodiments, a spectrum of fluorescence light (including, but not limited to, the NADH fluorescence) reflected from the illuminated tissue may be collected to distinguish tissue type. In some embodiments, the tissue is iUuminated with light having a wavelength between about 300 nm and about 400 nm. In some embodiments, a level of the reflected light having a wavelength between about 450 nm and 470 nm is monitored. In some embodiments, the monitored spectrum may be between 410 nm and 520 nm. Additionally or alternatively, a wider spectrum may be monitored, such as, by way of a non-limiting example, between 375 nm and 575 nm. In some embodiments, the NADH fluorescence spectrum and a wider spectrum may be displayed to user simultaneously. In some embodiments, the lesion may be created by ablation energy selected from the group consisting of radiofrequency (RF) energy, microwave energy, electrical energy, electromagnetic energy, cryoenergy, laser energy, ultrasound energy, acoustic energy, chemical energy, thermal energy and combinations thereof. In some embodiments, the processor may start (either automatically or by prompting the user) the procedure when a NADH fluorescence peak is detected so it can be monitored throughout the procedure. As noted above, these methods may be used in combination with other diagnostic methods, such as ultrasound monitoring.

[0043] System: Catheter

[0044] The catheter 140 may be based on a standard ablation catheter with accommodations for the optical fibers for illumination and spectroscopy, as discussed above. In some embodiments, the catheter 140 is a steerable, irrigated RF ablation catheter that can be delivered through a sheath to the endocardial space via a standard transseptal procedure and common access tools. On the handle of the catheter 147, there may be connections for the standard RF generator and irrigation system 170 for therapy. The catheter handle 147 also passes the optical fibers that are then connected to the diagnostic unit to obtain the tissue measurements.

[0045] Referring back to FIG. 1A, the catheter 140 includes a catheter body 142 having a proximal end 144 and a distal end 146. The catheter body 142 may be made of a biocompatible material, and may be sufficiently flexible to enable steering and advancement of the catheter 140 to a site of ablation. In some embodiments, the catheter body 142 may have zones of variable stiffness. For example, the stiffness of the catheter 140 may increase from the proximal end 144 toward the distal end 146. In some embodiments, the stiffness of the catheter body 142 is selected to enable delivery of the catheter 140 to a desired cardiac location. In some embodiments, the catheter 140 can be a steerable, irrigated radiofrequency (RF) ablation catheter that can be delivered through a sheath to the endocardial space, and in the case of the heart's left side, via a standard transseptal procedure using common access tools. The catheter 140 may include a handle 147 at the proximal end 144. The handle 147 may be in communication with one or more lumens of the catheter to allow passage of instruments or materials through the catheter 140. In some embodiments, the handle 147 may include connections for the standard RF generator and irrigation system 170 for therapy. In some embodiments, the catheter 140 may also include one more adaptors configured to accommodate the optical fiber for illumination and spectroscopy.

[0046] In reference to FIG. 1 A, at the distal end 146, the catheter 140 may include a distal tip 148, having a side wall 156 and a front wall 158. The front wall 158 may be, for example, flat, conical or dome shaped. In some embodiments, the distal tip 148 may be configured to act as an electrode for diagnostic purposes, such as for electrogram sensing, for therapeutic purposes, such as for emitting ablation energy, or both. In some embodiments where ablation energy is required, the distal tip 148 of the catheter 140 could serve as an ablation electrode or ablation element.

[0047] In the embodiments where RF energy is implemented, the wiring to couple the distal tip 148 to the RF energy source (external to the catheter) can be passed through a lumen of the catheter. The distal tip 148 may include a port in communication with the one or more lumens of the catheter. The distal tip 148 can be made of any biocompatible material. In some embodiments, if the distal tip 148 is configured to act as an electrode, the distal tip 148 can be made of metal, including, but not limited to, platinum, pktinum-iridium, stainless steel, titanium or similar materials.

[0048] In reference to FIG. 2A, an optical fiber or an imaging bundle ISO may be passed from the visualization system 120, through the catheter body 142, and into an illumination cavity or compartment 152, defined by the distal tip 148. The distal tip 148 may be provided with one or more openings 154 for exchange of light energy between the illumination cavity 152 and tissue. In some embodiments, even with multiple openings 154, the function of the distal tip 148 as an ablation electrode is not compromised. The openings may be disposed on the front wall 156, on the side wall 158 or both. The openings 154 may also be used as irrigation ports. The light is delivered by the fiber 150 to the distal tip 148, where it Uluminates the tissue in the proximity of the distal tip 148. This illumination light is either reflected or causes the tissue to fluoresce. The light reflected by and fluoresced from the tissue may be gathered by the optical fiber 150 within the distal tip 148 and carried back to the visualization system 120. In some embodiments, the same optical fiber or bundle of fibers 150 may be used to both direct light outside the distal tip to illuminate tissue outside the catheter 140 and to collect light from the tissue.

[0049] In reference to FIG. 2A, in some embodiments, the catheter 140 may have a visualization lumen 161 through which the optical fiber 150 may be advanced through the catheter body 142. The optical fiber 150 may be advanced through the visualization lumen 161 into the illumination cavity 152 to iUuminate the tissue and receive reflected light through the opening 154. As necessary, the optical fiber 150 may be advanced beyond the illumination cavity 152 through the opening 154.

[0050] As shown in FIG. 2A and FIG. 2B, in addition to the visualization lumen 161, the catheter 140 may further include an irrigation lumen 163 for passing irrigation fluid from the irrigation system 170 to the openings 154 (irrigation ports) in the distal tip 148 and an ablation lumen 164 for passing ablation energy from the ablation therapy system 110 to the distal tip 148, such as, for example, by passing a wire through the ablation lumen 164 for RF ablation energy. It should be noted that the lumens of the catheter may be used for multiple purposes and more than one lumen may be used for the same purpose. In addition, while FIG. 2A and FIG. 2B show the lumens being concentric other configurations of lumens may be employed.

[00S1] As shown in FIG. 2A and FIG. 2B, in some embodiments, a central lumen of the catheter may be utilized as the visualization lumen 161. In some embodiments, as shown in FIG. 2C, the visualization lumen 161 may be off set in relation to the central access of the catheter 140.

[0052] In some embodiments, the light may also be directed radially out of the openings 154 in the side wall 156, alternatively or additionally to being directed through the opening in the front wall 158. In this manner, the light energy exchange between the illumination cavity 152 and tissue may occur over multiple paths, axially, radially or both with respect to the longitudinal central axis of the catheter, as shown in FIG. 2E. This is useful when the anatomy will not allow the catheter tip to be orthogonal to the target site. It may also be useful when increased illumination is required. In some embodiments, additional optical fibers 150 may be used and may be deflected in the radial direction with respect to the catheter 140 to allow the illumination and returned light to exit and enter along the length of the catheter.

[0053] In reference to FIG. 2D, to enable the light energy exchange between the illumination cavity 152 and tissue over multiple paths (axially and radially with respect to the longitudinal central axis of the catheter), a light directing member 160 may be provided in the illumination cavity 152. The light directing member 160 may direct the iUumination light to the tissue and direct the light returned through the one or more openings 154 within the distal tip 148 to the optical fiber 150. The light directing member 160 may also be made from any biocompatible material with a surface that reflects light or can be modified to reflect light, such as for example, stainless steel, platinum, platinum alloys, quartz, sapphire, fused silica, metallized plastic, or other similar materials. The light directing member 160 may be conical (i.e. smooth) or faceted with any number of sides. The light directing member 160 may be shaped to bend the light at any desired angle. In some embodiments, the light directing member 160 may be shaped to reflect the light only through the one or more openings. In some embodiments, the material for the light directing member 160 is chosen from materials that do not fluoresce when exposed to illumination between 310 nm to 370 ran. In some embodiments, as shown in FIG. 2D, the light directing member 160 may include one or more holes 162 through the center line of the mirror, which allow illumination and reflected light to pass in both directions axially, directly in line with the catheter 140. Such an axial path may be useful when the distal-most surface of the distal tip 148 is in contact with the anatomy. The alternate radial paths, as shown in FIG. 2E, may be useful when the anatomy will not allow the distal-most surface of the distal tip 148 to be in contact with the target site as is sometimes the case in the left atrium of the patient during pulmonary vein isolation procedures, common in treating atrial fibrillation. In some embodiments, in all pathways, lensing may not be required and the optical system is compatible with the irrigation system 170 as the light passes through the cooling fluid, which is often saline. The irrigation system 170 may also serve to flush the blood from the holes 162, thus keeping the optical components clean.

[0054] Methods of Use

[00S5] In some embodiments, methods for monitoring tissue ablation are provided. Such methods may provide a real time visual feedback on various factors that can impact lesion formation by displaying the level of NADH fluorescence, as is described below.

[00S6] In some embodiments, the methods include applying ablation energy to a tissue to form a lesion in the tissue, illuminating the tissue with UV light to excite NADH in the tissue, wherein the tissue is illuminated in a radial direction, an axial direction, or both, monitoring a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level, and stopping ablation of the tissue when the level of NADH fluorescence reaches the predetermined lower level. In some embodiments, a spectrum of fluorescence light (including, but not limited to, the NADH fluorescence) reflected from the illuminated tissue may be collected to distinguish tissue type. In some embodiments, the tissue is iUuminated with light having a wavelength between about 300 nm and about 400 nm. In some embodiments, a level of the reflected light having a wavelength between about 450 nm and 470 nm is monitored. In some embodiments, the monitored spectrum may be between 410 nm and 520 nm. Additionally or alternatively, a wider spectrum may be monitored, such as, by way of a non-limiting example, between 375 nm and 575 nm. In some embodiments, the lesion may be created by ablation energy selected from the group consisting of radiofrequency (RF) energy, microwave energy, electrical energy, electromagnetic energy, cryoenergy, laser energy, ultrasound energy, acoustic energy, chemical energy, thermal energy and combinations thereof. In some embodiments, the methods may be started when a NADH fluorescence peak is detected so it can be monitored throughout the procedure. As noted above, these methods may be used in combination with other diagnostic methods, such as ultrasound monitoring.

[0057] Pre-Lesion ATiatnmical Assessment

[0058] Illumination of cardiac tissue at wavelengths of about 350 to about 360 nm can elicit an auto-fluorescence response from NADH present in the mitochondria of myocardial cells. Variability of myocardial fNADH response can indicate that the catheter is positioned against tissue. In some embodiments, the entire spectral signature can be captured from 350 nm to 850 nm range, or as shown in FIG. 3 from 400 to 700 nm, with the peak fluorescence of NADH occurring around 460 nm. The blood in the circulatory systems is capable of absorbing the light and therefore no fluorescence can be detected while the catheter is in the blood pool, which would indicate no contact between the catheter and the tissue. As the catheter touches the myocardium a characteristic tissue fluorescence spectral signature is elicited, which would indicate good contact response. On the other hand, if the catheter is pushed with excessive force to cause tenting, the transient ischemia can result in an elevated fluorescence and the spectral signature shifts above the baseline. The use of such feedback may help reduce the risk of perforation during catheter ablation and manipulation, will help avoid ablation at sub-optimal tissue contact sites and hence decrease RF ablation time

[0059] Lesion Formation Assessment

[0060] The information content of the returned spectrum may be obtained in real-time during lesion formation. The analysis and display of the spectrum can add qualitative assessment of the lesion, as it forms in real-time. FIG. 4 shows the returned spectrum from an illumination source of 355nm during lesion formation. The fNADH peak is between about 450nm and 550nm. During ablation, the magnitude of the returned spectrum between approximately 450nm and 550nm drops significantly over time as the successful lesion forms. This effect is due to the reduction of metabolic activity and hence reduction of fNADH as the cells are ablated. This drop may be used as an indication when to stop ablation. In some embodiments, the ablation may be stopped upon reduction in the fNADH signal by 80% or more. In some embodiments, reduction in fNADH signal by over 50% and resultant achievement of steady state fNADH signal tor more than a specific period of time such as 5 or 10 seconds may be used as a stopping point In some embodiments, 60% or more reduction in fNADH signal over a specific period of time such as up to 10 seconds and resultant steady state fNADH signal for more than S seconds may be used.

[0061] In reference to FIG. 4, in some embodiments, the spectral signature may be collected over a broader spectrum. For example, the spectral pattern of collagenous tissue is different than the one seen on healthy myocardium. The peak of the spectrum shifts to the left when imaging over collagenous tissue. This may be used by the user to identify the area that is being treated as being mostly myocardium or being covered by collagen, which is harder to ablate.

[0062] FIG. 5 and FIG. 6 also illustrate this phenomenon during successful RF lesion formation on endocardial and epicardial surfaces respectively. In both sets of plots, the peak magnitude of the wavelengths that correlate to fNADH (450nm to 470nm) are normalized and plotted versus ablation time. As can be seen in FIG. 5, there is a precipitous drop in the peak magnitude within the first 10 seconds and a continued low level through the duration of the application of energy to the endocardium. FIG. 6 shows the same plot but with the RF energy applied to the epicardium. Again the effect is similar in both figures showing that the present systems and methods can be beneficial to technologies that ablate arrhythmias from either surface of the heart. This could be significant in that the lesion may be well formed in less time than originally thought and that continued application of energy could be excessive (see the discussion below regarding impedance). It has been well documented in the literature that excessive ablation energy to the blood pool or the tissue or both can lead to dramatically negative outcomes and procedural complications such as intracardiac steam pops, endocardial crater formation (endocardial denudation of the inner lining of the heart), thrombus (clot) formation, embolism (migration of clots), stroke, and even death. The ability to limit energy delivery while ensuring optimal or even adequate lesion is thus beneficial in cardiac ablation.

[0063] In reference to FIG. 7A, FIG. 7B and FIG. 7C, in some embodiments, the spectral signature may be monitored to determine catheter stability during lesion formation. For example, as shown in FIG. 7 A, a smooth response corresponds to a stable catheter, as the gradual reduction in fNADH intensity indicates the formation of the ablation lesion over time. FIG. 7B shows a sharper, more noisy response, which corresponds to intermittent or shifting tip of the catheter in relation to tissue. FIG. 7C shows that catheter movement can also be picked up during ablation based on the fNADH, a transient shift in fNADH is seen when the catheter jumps to a different location.

[0064] Post-Lesion Anatomical Assessment

[0065] Finally, the ability to interrogate tissue to identify areas of poor ablation or inadequate lesion formation, namely residual gaps and electrically conducting zones, is a challenge in today's ablation paradigm. It is only feasible electrically with multiple catheters and is time consuming, laborious and utilizes considerable fluoroscopy (x-ray radiation exposure). This system can optically and visually identify gaps without electrical interrogation yielding faster, safer and better identification of areas that were missed in a previous ablation. This has significant implications in both acute procedures as well as repeat ablations, or cases of previously failed ablation procedures.

[0066] FIG. 8A and FIG. 8B show how the systems and methods of the present disclosure can be used to evaluate previously formed lesions, whether they are chronic or freshly made. FIG. 8A shows a sequential schematic representation of a catheter tip as it moves from healthy myocardium to the margin of an existing lesion and then over the center of the existing lesion. FIG. 8B shows a composite of the normalized peak magnitude of the optical spectrum returned under 355nm illumination. The wavelengths central to fNADH has a significant difference in signal amplitude correlating perfectly to the state of the myocardium in contact with the tip of the catheter.

[0067] Comparison to Impedance

[0068] By way of a non-limiting example, FIG. 9 contrasts the fNADH response and therapy impedance over the duration of lesion formation. Impedance is a standard indicator used during ablation procedures throughout the world. It is typically measured from the tip of the catheter to the ablation ground pad adhered to the patient's torso. Physicians expect to see a drop of approximately 10 to 15 ohms in the first 2 or 3 seconds after the onset of ablation energy. If the impedance does not drop, the physician knows that this is likely due to poor catheter contact with the myocardium and the lesion attempt is aborted and the catheter repositioned. The methods described above may be used to ensure better contact between the catheter and the tissue. If the impedance does drop and maintain a new level, the physician continues applying lesion-forming energy typically for a fixed time (30 to 60 seconds or more). If the impedance rises over time, it is an indicator of potential overheating at the tip of the catheter and if unabated can result in dangerous situations of steam formation resulting in cardiac wall rupture or char buildup on the tip of the catheter that could dislodge and become an embolic body.

[0069] As shown in FIG. 9, the signal-to-noise ratio (SNR) of the fNADH optical response as compared to therapy impedance SNR would suggest that fNADH is a good indicator of lesion-formation quality. The change in amplitude of the fNADH magnitude is approximately 80% where the same drop in normalized impedance is less than 10%. This comparison of optical signature to impedance also indicates a more direct reflection of the activity in the tissue relative to impedance since the impedance often is a much larger reflection of the electrical path from the electrode to the ground pad through the blood pool. Using the optical approach, all of the light signature is from the tissue and none originates from the blood pool if good contact is maintained. As such, the optical signature is much more highly reflective of the activity in the tissue than the impedance signature.

[0070] The foregoing disclosure has been set forth merely to illustrate various non-limiting embodiments of the present disclosure and is not intended to be limiting. Since modifications of the disclosed embodiments incorporating the spirit and substance of the disclosure may occur to persons skilled in the art, the presently disclosed embodiments should be construed to include everything within the scope of the appended claims and equivalents thereof. All references cited in this application are incorporated herein by reference in their entireties.

Claims

CLAIMS What is claimed is:

1. A method for monitoring tissue ablation comprising:

applying ablation energy to a tissue to form a lesion in the tissue; illuminating the tissue to excite NADH in the tissue, wherein the tissue is illuminated in a radial direction, an axial direction, or both; monitoring a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level; and stopping ablation of the tissue when the level of NADH fluorescence reaches the predetermined lower level.

2. The method of claim 1 further comprising collecting a spectrum of fluorescence light reflected from the illuminated tissue to distinguish tissue type.

3. The method of any one of claims 1-2 wherein the tissue is illuminated with light having a wavelength between about 300 nm and about 400 nm.

4. The method of any one of claims 1-3 further comprising monitoring a level of the reflected light having a wavelength between about 4S0 nm and 470 nm.

5. The method of any one of claims 1-4 wherein the ablation energy is selected from the group consisting of radiofrequency (RF) energy, microwave energy, electrical energy, electromagnetic energy, cryoenergy, laser energy, ultrasound energy, acoustic energy, chemical energy, thermal energy and combinations thereof.

6. The method of any one of claims 1-5 further comprising advancing a catheter to the tissue, the catheter comprising:

a catheter body;

a distal tip positioned at a distal end of the catheter body for delivering ablation energy to the tissue, the distal tip defining an illumination cavity having one or more openings for exchange of light between the illumination cavity and the tissue; and one or more optical fibers extending through the catheter body into the illumination cavity of the distal tip, the one or more optical fibers being in communication with a light source and a light measuring instrument to illuminate the tissue and to relay light energy reflected from the tissue to the light measuring instrument.

7. The method of any one of claims 1-6 further comprising illuminating the tissue in a radial direction and an axial direction with respect to a longitudinal axis of a catheter.

8. The method of any one of claims 1-7 further comprising providing a real time visual feedback about the lesion formation by displaying the level of NADH fluorescence.

9. The method of any one of claims 1-8 further, wherein the ablation energy is applied when a NADH fluorescence peak is detected.

10. The method of any one of claims 1-10 further comprising performing an ultrasound evaluation of tissue in combination with monitoring the level of NADH fluorescence.

11. A system for monitoring tissue ablation comprising:

a catheter comprising:

a catheter body; and

a distal tip positioned at a distal end of the catheter body, the distal tip defining an illumination cavity having one or more openings for exchange of light energy between the illumination cavity and a tissue;

an ablation system in communication with the distal tip to deliver ablation energy to the distal tip;

a visualization system comprising a light source, a light measuring instrument, and one or more optical fibers in communication with the light source and the light measuring instrument and extending through the catheter body into the illumination cavity of the distal tip, wherein the one or more optical fibers are configured to pass light energy in and out of the illumination chamber;

a processor in communication with an ablation energy source, the light source and the light measuring instrument, the processor being programmed to: collect light reflected from a tissue illuminated to excite NADH in the tissue, while ablation energy is being applied to the tissue to form a lesion in the tissue; monitor a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level; and cause ablation of the tissue to stop when the level of NADH fluorescence reaches the predetermined lower level.

12. The system of claim 11 wherein the tissue is illuminated with light having a wavelength between about 300 urn and about 400 ma

13. The system of any one of claims 11-12 wherein the processor monitors a level of the reflected light having a wavelength between about 4S0 nm and about 470 nm.

14. The system of any one of claims 11-13 wherein the ablation energy is selected from the group consisting of radiofrequency (RF) energy, microwave energy, electrical energy, electromagnetic energy, cryoenergy, laser energy, ultrasound energy, acoustic energy, chemical energy, thermal energy and combinations thereof.

15. The system of any one of claims 11-14 wherein the catheter is configured to iUuminate the tissue in a radial direction and an axial direction with respect to a longitudinal axis of the catheter.

16. The system of any one of claims 11-15 further comprising an irrigation system for irrigation the one or more openings.

17. The system of any one of claims 11-16 wherein the catheter further comprises one or more ultrasound transducers and one or more electromagnetic location sensors and the system further comprises an ultrasound system in communication with the one or more ultrasound transducers for ultrasound evaluation of the tissue.

18. The system of any one of claims 11-17 wherein the catheter further includes one or more electromagnetic location sensors and the system further includes a navigation system in communication with the one or more electromagnetic location sensors for locating and navigating the catheter.

19. The system of any one of claims 11-18 wherein the system applies the ablation energy when a NADH fluorescence peak is detected.

20. The system of any one of claims 11-19 wherein the system is configured to collect a spectrum of fluorescence light reflected from the illuminated tissue to distinguish tissue type.